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Study shows hydroxychloroquine’s harmful effects on heart rhythm

Study shows hydroxychloroquine’s harmful effects on heart rhythm

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Credit: Georgia Tech School of Physics

The malaria drug hydroxychloroquine, which has been promoted as a potential treatment for Covid-19, is known to have potentially serious effects on heart rhythms. Now, a team of researchers has used an optical mapping system to observe exactly how the drug creates serious disturbances in the electrical signals that govern heartbeat.

The research, reported May 29 in the journal Heart Rhythm, found that the drug made it “surprisingly easy” to trigger worrisome arrhythmias in two types of animal hearts by altering the timing of the electrical waves that control heartbeat. While the findings of animal studies can’t necessarily be generalized to humans, the videos created by the research team clearly show how the drug can cause cardiac electrical signals to become dysfunctional.

“We have illustrated experimentally how the drug actually changes the waves in the heart, and how that can initiate an arrhythmia,” said Flavio Fenton, a professor in the School of Physics at the Georgia Institute of Technology and the paper’s corresponding author. “We have demonstrated that with optical mapping, which allows us to see exactly how the waveform is changing. This gives us a visual demonstration of how the drug can alter the wave propagation in the heart.”

What the team saw was an elongation of the T wave, a portion of the heart cycle during which voltages normally dissipate in preparation for the next beat. By extending the QT portion of one wave cycle, the drug sets the stage for disturbances in the next wave, potentially creating an arrhythmia. Such disturbances can transition to fibrillation that interferes with the heart’s ability to pump.

The ability to easily trigger disturbances known as “long QT” reinforces cautions about using hydroxychloroquine (HCQ) in humans – particularly in those who may have heart damage from Covid-19, cautioned Dr. Shahriar Iravanian, a co-author of the paper and a cardiologist in the Division of Cardiology, Section of Electrophysiology, at Emory University Hospital.

“The hearts used in the study are small and very resistant to this form of arrhythmia,” Iravanian said. “If we had not seen any HCQ-induced arrhythmias in this model, the results would not have been reassuring. However, in reality, we observed that HCQ readily induced arrhythmia in those hearts. This finding is very concerning and, in combination with the clinical reports of sudden death and arrhythmia in Covid-19 patients taking HCQ, suggests that the drug should be considered a potentially harmful medication and its use in Covid-19 patients be restricted to clinical trial settings.”

Georgia Tech postdoctoral fellow Ilija Uzelac administered HCQ to the animal hearts – one from a guinea pig and one from a rabbit – while quantifying wave patterns changing across the hearts using a high-powered, LED-based optical mapping system. Voltage-sensitive fluorescent dyes made the electrical waves visible as they moved across the surface of the hearts.

“The effect of the arrhythmia and the long QT was quite obvious,” said Uzelac. “HCQ shifts the wavelengths to larger values, and when we quantified the dispersion of the electrical current in portions of the heart, we saw the extension of the voltage across the tissue. The change was very dramatic comparing the waveforms in the heart with and without the HCQ.”

The drug concentration used in the study was at the high end of what’s being recommended for humans. HCQ normally takes a few days to accumulate in the body, so the researchers used a higher initial dose to simulate the drug’s effect over time.

In a normal heartbeat, an electrical wave is generated in specialized cells of a heart’s right atrium. The wave propagates through the entire atria and then to the ventricles. As the wave moves through the heart, the electrical potential created causes calcium ions to be released, which stimulates contraction of the heart muscle in a coordinated pattern.

Drugs such as HCQ modify the properties of these ion channels and inhibit the flow of potassium currents, which prolongs the length of the electrical waves and creates spatial variations in their properties. Ultimately, that can lead to the development of dangerously rapid and dysfunctional heart rhythms.

“The wavelength becomes less homogeneous and that affects the propagation of additional waves, producing sections of the heart where the waves do not propagate well,” Fenton said. “In the worst case, there are multiple waves going in different directions. Every section of the heart is contracting at a different time, so the heart is just quivering. At that point, it can no longer pump blood throughout the body.”

Patients taking HCQ for diseases such as lupus and rheumatoid arthritis rarely suffer from arrythmia because the doses they take are smaller than those being recommended for Covid-19 patients, Iravanian said.

“Covid-19 patients are different and are at a much higher risk of HCQ-induced arrhythmia,” he said. “Not only is the proposed dose of HCQ for Covid-19 patients two to three times the usual dose, but Covid-19 has effects on the heart and lowers potassium levels, further increasing the risk of arrythmias.”

Fenton and his colleagues have already begun a new study to evaluate the effects of HCQ with the antibiotic azithromycin, which has been suggested as a companion treatment. Azithromycin can also cause the long QT effect, potentially increasing the impact on Covid-19 patients.

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The study, which was supported by grants from the National Institutes of Health and National Science Foundation, was also coauthored by Dr. Hiroshi Ashikaga from Johns Hopkins University School of Medicine; Dr. Neal Bathia from the Division of Cardiology, Section of Electrophysiology at Emory University Hospital; Conner Herndon, Abouzar Kaboudian, and James C. Gumbart from the Georgia Tech School of Physics, and Elizabeth Cherry from the Georgia Tech School of Computational Science and Engineering.

This research is supported by the National Institutes of Health under award number 1R01HL143450-01 and the National Science Foundation under grant 1446675. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Science Foundation.

Media Contact
John Toon
jtoon@gatech.edu

Related Journal Article

http://dx.doi.org/10.1016/j.hrthm.2020.05.030

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Economics

New Provisional CDC Suicide Death Data Is a Call to Action to Double Down on Suicide Prevention Efforts

New Provisional CDC Suicide Death Data Is a Call to Action to Double Down on Suicide Prevention Efforts
PR Newswire
NEW YORK, Sept. 30, 2022

NEW YORK, Sept. 30, 2022 /PRNewswire/ — The Centers for Disease Control and Prevention today releases prov…

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New Provisional CDC Suicide Death Data Is a Call to Action to Double Down on Suicide Prevention Efforts

PR Newswire

NEW YORK, Sept. 30, 2022 /PRNewswire/ -- The Centers for Disease Control and Prevention today releases provisional data on suicide deaths for the year 2021. According to the new data, suicide deaths in the United States increased from 45,979 to 47,646 (4%) between the years 2020 and 2021.

The American Foundation for Suicide Prevention (AFSP), the nation's largest suicide prevention organization, released the following statement regarding the CDC's provisional data which do not include final national suicide rates for the year 2021.

"At AFSP we understand how devastating and painful it is to lose a loved one to suicide. This CDC provisional suicide data invigorates our resolve to continue fighting so that we can see a day when suicide does not exist. Despite the data indicating an increase in suicide deaths in 2021, we remain hopeful that our public education and advocacy efforts are making a difference. While this new provisional data is concerning, the data shows that fewer people died by suicide in 2021 than in 2018.

As people interpret the newly released CDC report, it's important to remember that suicide is complex, and we are still understanding through research how societal factors and historical context impact suicide at an individual level. 

  • The data does not explain what contributed to the overall reported increases in suicide deaths. Suicide is complex, risk is dynamic, and an individual's personal risk factors combined with precipitants such as experiences with isolation, depression, anxiety, economic stress, suicidal ideation, and access to lethal means may lead to periods of increased risk.
  • Suicide did not increase at the same rate for every age group. Rates remained relatively stable for females of all age groups and males ages 55 to 64 but increased for males in other age groups. The largest increase in the suicide rate occurred among males ages 15-24 – an 8% increase. Because the teen years are a time when we see the onset of mental health concerns as well as more suicide attempts, this makes early detection and prevention efforts for youth critical. Note: This being provisional data, more information is needed to understand within-group differences. 2020 data indicates higher rates among males ages 20-24 than males ages 15-19.
  • Further analysis of this provisional data is needed to understand impact in terms of race, ethnicity and other factors beyond age and sex. This provisional data does not include race, ethnicity, or geographical data. We also need much more research to consider suicide risk through the lens of social determinants such as income, access to health care, and other disparities in health and psychosocial stressors.
  • The COVID-19 pandemic and its lasting effect on our nation's mental health are far from over. We cannot yet fully understand the entire impact of the pandemic on suicide deaths for the longer-term as it takes years to collect comprehensive data and analyze it in a meaningful way. Research has shown that people tend to come together during traumatic events initially and this can serve as a protective factor against suicide, though this societal cohesion may not persist as time passes. This is why sustained prevention education efforts and advocacy are needed. Protective factors that were activated during the pandemic – like community cohesion, normalizing the national dialog around mental health, and the increase in seeking help – can continue to help mitigate suicide risk and can likely save many more lives. It is certainly a time to make the implementation of suicide prevention efforts that are evidence-informed a top priority with an eye toward taking them to the broadest scale possible.

At AFSP, we remain dedicated to our mission of saving lives and bringing hope to those affected by suicide through efforts like:

  • Raising awareness and engaging state and federal policymakers to realize the full vision of 988, ensuring that all individuals have access to the new 988 suicide and crisis lifeline and a full continuum of community crisis services. 988 will continue to help increase public access to mental health and suicide prevention resources, encourage help-seeking for those who may be struggling with their mental health or have a loved one who is, and establish a comprehensive continuum of crisis care in our country.
  • Continuing to achieve the goal of reducing the annual suicide rate by 20% by 2025 through Project 2025 by partnering with organizations to embrace stronger evidence-based suicide prevention practices in critical settings like healthcare systems, emergency departments, corrections systems, and the firearms community where coordinated suicide prevention strategies can have a dramatic impact on saving lives. Suicide risk screening coupled with risk-reducing steps in healthcare settings, collaborating with large health systems and key accrediting professional organizations, can improve the acceptance and adoption of screening and preventive interventions as the standard of care.
  • Demanding more accessible and affordable mental health care: We all should have easy access to mental health care on a regular, ongoing basis. Assessment and treatment for mental health conditions must be accessible, culturally appropriate and effective. This kind of care can save lives, but only if individuals at risk can afford to obtain care. AFSP supports efforts to ensure that individuals receive the same insurance coverage for their mental health as their physical health, also known as "mental health parity."

American Foundation for Suicide Prevention creates a culture that's smart about mental health through education and community programs, developing suicide prevention through research and advocacy, and providing support for those affected by suicide. Led by CEO Robert Gebbia and headquartered in New York, with an Advocacy office in Washington, DC, AFSP has local chapters in all 50 states and Puerto Rico with programs and events nationwide. Learn more about AFSP in its latest Annual Report, and join the conversation on suicide prevention by following AFSP on Facebook, Twitter, Instagram, and YouTube.

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SOURCE American Foundation for Suicide Prevention

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Spread & Containment

Computers calling time on isolation

Kyoto–Across the world, many people infected with Covid-19 have been made to completely isolate from others in order to avoid passing on the infection….

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Kyoto–Across the world, many people infected with Covid-19 have been made to completely isolate from others in order to avoid passing on the infection. Some countries still recommend minimum isolation periods for as long as 10 days from when patients start to develop Covid-19 symptoms.

Credit: LAIMAN

Kyoto–Across the world, many people infected with Covid-19 have been made to completely isolate from others in order to avoid passing on the infection. Some countries still recommend minimum isolation periods for as long as 10 days from when patients start to develop Covid-19 symptoms.

Professor Shingo Iwami, affiliated with Kyoto University’s Mathematical Biology Laboratory at the Institute Advanced Study of Human Biology (WPI-ASHBi) says, “Although a long time for isolation reduces the overall risk of patients passing on the infection, there will always be patients who recover early and have to accept several days of redundant isolation while no longer posing an infection risk. We would like to calculate a way to reduce this unnecessary disruption in people’s lives as well as the broader losses for the economy.”

Writing in the journal Nature Communications, an international team of scientists, led by Iwami, has reported a simulation of the potential risks and benefits of ending an individual’s isolation early using antigen tests instead of isolating patients for a fixed time. They call for more sensitive and regular antigen testing to help reduce isolation periods for patients recovering from Covid-19.

The team decided to base their model on antigen rather than PCR testing, trading sensitivity for short turn-around time, low cost, and practicality. Iwami explains that although antigen tests do have a risk of generating “false-negatives” and fail to detect individuals who could still be infectious, there are clear benefits to getting results within an hour rather than waiting a day.

Their model accounts for the sensitivity of antigen tests as well as factors like the amount of virus in a patient that makes them infectious. These are then balanced against the acceptable risk of missing unrecovered and potentially infectious patients, by letting them out of isolation early.

Using their model, the team compared different scenarios to identify the best strategy. For example, the model projects that letting a recovering patient leave isolation after 2 consecutive negative results on 2 days in a row would spend 3.9 days of redundant isolation after their recovery. But under these conditions 1 in 40 patients would continue to pose an infection risk.

More conservative approaches might increase the burden on patients by requiring more than 2 consecutive negative test results of antigen tests.

Iwami says, “The epidemic has still not completely subsided, and we are living with a lot of uncertainty with regard to new variants of the virus. Antigen tests could help, but there is also a real need for worldwide systematic guidelines that simultaneously reduce risks and burdens. We hope this simulator will help doctors and policy makers meet those demands.”

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About WPI-ASHBi https://ashbi.kyoto-u.ac.jp/
Institute for the Advanced Study of Human Biology (ASHBi) was launched in October 2018 with funding from the World Premier International Research Center Initiative (WPI) Program of the Ministry of Education, Culture, Sports, Science and Technology (MEXT). The Institute inaugurated with 18 principal investigators (PIs) to create and promote human biology to elucidate key principles of human traits, including disease states. The Institute will perform interdisciplinary research between biology and mathematics (machine learning and topological data analysis) and between biology and humanities/social sciences (bioethics and philosophy on life), respectively. The Institute implements three research development cores for cutting-edge single-cell genome information analysis, primate genome editing, and non-human primate phenotype analysis, respectively. The Institute establishes a link with international institutions such as the EMBL, University of Cambridge, and Karolinska Institutet, creating a stratified organization for research promotion and strengthening its international profile.


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PA’s Southeast Regional Road to Recovery Strengthened by Biden-Harris Administration

PA’s Southeast Regional Road to Recovery Strengthened by Biden-Harris Administration
PR Newswire
PHILADELPHIA, Sept. 29, 2022

The American Rescue Plan is behind three significant economic and workforce investments that will reshape the future for B…

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PA's Southeast Regional Road to Recovery Strengthened by Biden-Harris Administration

PR Newswire

The American Rescue Plan is behind three significant economic and workforce investments that will reshape the future for Berks, Bucks, Chester, Delaware, Montgomery, and Philadelphia Counties     

PHILADELPHIA, Sept. 29, 2022 /PRNewswire/ -- Today, the White House hosted a half-day forum to acknowledge the positive micro effects of investments made from the Biden-Harris Administration, many allocated to support a post-pandemic economic revival. Distinguished leaders from across the Commonwealth were invited to convene in Washington, D.C. for the "Communities in Action: Building a Better Pennsylvania" forum, an event designed to share how the American Rescue Plan, the Inflation Reduction Act, and Pennsylvania's Bipartisan Infrastructure Law is strengthening PA's economic recovery efforts.   

Today at The White House, I had an opportunity to meet with leaders from all across our state who are working together for progress.

For Southeast PA, federal investments look like the Good Jobs Challenge, a $22.8M grant award that will invest in building talent pipelines into the life sciences, energy, and construction industries; the Apprenticeship Building America grant award, a $4.7M investment which will expand registered apprenticeship opportunities in high-demand industries such as education, IT, and healthcare; and the CAREER Dislocated Worker Grant of $3M, which addresses specific challenges for dislocated workers, providing unemployed individuals with the extra support they need to compete in today's labor market.

"After a year and a half of economic recovery in Pennsylvania, the southeast region remains focused on its future," said H. Patrick Clancy, president and CEO at Philadelphia Works. "Today at The White House, I had an opportunity to meet with leaders from all across our state who are working together for progress. Through job creation, improved workforce training programs, and innovative solutions we will do our part to build a better America."

Through the combined efforts of regional industry and labor leaders and the Biden Administration's prioritization of economic recovery, the Southeast Philadelphia region is well positioned to support both career seekers and businesses to thrive now and for generations to come.

About Philadelphia Works

Philadelphia Works invests in solutions and services to grow Philadelphia's economy by connecting employers to workforce talent and career seekers to jobs. We influence the public policies that support economic growth and optimize funding and resources to invest in regional solutions to build a skilled and thriving workforce. For more information about our dedicated board members and staff, workforce research, labor market data, services, and initiatives, and to view success stories, please visit philaworks.org.

Contact: Dawn Thomas
Director, Communications and Outreach
newsroom@philaworks.org
Voicemail: 215-557-2587

View original content to download multimedia:https://www.prnewswire.com/news-releases/pas-southeast-regional-road-to-recovery-strengthened-by-biden-harris-administration-301637384.html

SOURCE Philadelphia Works

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